Acupuncture is appealing pain control technique in that it can evoke endogenous analgesic mechanisms by minimally invasive means. The mechanisms of acupuncture are not well understood, however, and one of the major problems impeding this understanding is a lack of proper experimental models. The present proposal describes a model of electroacupuncture (EA)- induced analgesia in ankle sprain pain. This model gives a repeatable and quantifiable index of persistent pain in the ankle joint and the preliminary data show that acupuncture at a remote site produces long-lasting analgesia in this model. This is shown by the finding the EA results in about 40% recovery of weight bearing by the hind limb with ankle sprain. This reproducibility and susceptibility to acupuncture will allow one to pursue the neural mechanisms of this phenomenon in considerably greater detail than has previously been possible. Four specific aims are proposed. Aim 1 is to investigate the origin and the fiber size group of afferent nerve fibers mediating EA analgesia using behavioral testing and electrophysiological techniques. Aim 2 is to test if EA induces NE release in the spinal cord by a descending system using pharmacological and neurochemical methods. Aim 3 is to test if ankle sprain induces central sensitization in the spinal cord as well as sensitization of peripheral nociceptors and EA reduces the level of central sensitization. Aim 4 is to test if the key CNS structures activated by EA is the anterior pretectal nucleus (APtN), which projects to brainstem noradrenergic cell groups to release NE in the spinal cord. Successful completion of this proposal will unveil important mechanisms underlying acupuncture analgesia in ankle sprain pain. This knowledge can then be applied to acupuncture analgesia in other forms of painful conditions, thereby gaining the insight to establish a maximally effective means of utilizing this endogenous analgesic system. An understanding of these mechanisms is necessary if acupuncture is to move into the mainstream of medical therapy.